The theme of this program project is to develop ultrasensitive biomarkers of exposure and genetic effects to carcinogens, as an index of individual exposure, and to investigate the hydrogeological and ecological factors which contribute to variability in human population exposure. The program consists of six integrated research projects, research cores on chemistry and epidemiology, and an administrative/training core. Vinyl chloride (VC), pentachlorophenol (PCP) and polynuclear aromatic hydrocarbons (PAH) have been selected for investigation due to their widespread potential for human exposure. Three biomedical projects will concentrate on developing biomarkers of exposure and effect in order to examine their utility in future epidemiology studies. Project 1 will develop ultrasensitive methods for quantifying the DNA adducts of VC and PCP and conduct molecular dosimetry studies. Project 2 will determine the mutational spectra of VC and PCP in human cells and animals as an early biomarker of genetic effect. Project 3 will utilize new techniques for identifying and quantifying hemoglobin and albumin adducts of VC and PCP. Three hydrogeologic projects will examine the fate and transport of chemicals to identify critical factors that determine the extent of human exposure. Project 4 will examine microbial transformation of chemicals in the subsurface environment that can affect both toxicity and mobility. Project 5 will investigate multicomponent, multiphase flow and transport processes in subsurface systems. These data will be useful in developing stochastic modeling in Project 6, to better predict the spatial variability of contaminant transport. These models will be of immense value, both in selecting populations for investigation of exposure-response relationships and, ultimately, in predicting human exposure based on the hydrogeologic factors identified. The biomarker and engineering components of this program project are designed so that their data and methods will become interactive during the second half of the project. The biomarkers will be evaluated over a large exposure range to define their limits of detection. The engineering components will identify likely environmental exposure scenarios. By frequent interactions between these two groups, we will develop much greater insight into the feasibility of future epidemiology studies and requirements for additional methods development and modeling. This program project will also provide strong interdisciplinary training for 19 pre- and post-doctoral fellows in environmental sciences by combining coursework, seminars and research in environmental health sciences, hydrogeological engineering, and microbial ecology.